Visna is a slow infection of sheep caused by a virus closely related to RNA tumor viruses. This proposal addresses two issues: 1) persistence of the virus after a full immune response has been achieved, 2) the regulation of virus production which causes the disease to evolve so slowly. Persistence is hypothesized to derive from the virus' ability to reside for extended periods inside the cell as a provirus. Slowness is considered to be a consequence of altered synthesis in vivo of viral DNA, RNA or proteins. Data relevant to these hypotheses will be sought by comparing the synthesis of viral DNA and RNA in sheep choroid plexus cells infected with visna virus in vivo and in vitro. In order to quantitate viral nuclei acid synthesis in infected tissues, considerable effort will be devoted to in situ hybridization. BIBLIOGRAPHIC REFERENCES: Haase, A. T., Stowring, L. S., Narayan, O., Griffin, D., Price, D. The Slow Persisent Infection Caused by Visna Virus: The Role of Lysogeny. Science, 195: 175-177(1977). Haase, A. T., Stowring, L. S., Ventura, P. E., Traynor, B., Johnson, K., Swoveland, P., Smith, M., Britten-Darnall, M., Faras, A., Narayan, O. The Role of DNA Intermediates in Persistent Infections Caused by RNA Viruses. Mircrobiol., in press (1977).